title: Murine melanoma-infiltrating dendritic cells are defective in antigen presenting function regardless of the presence of CD4CD25 regulatory T cells.
abstract: Tumor-infiltrating dendritic cells are often ineffective at presenting tumor-derived antigen in vivo, a defect usually ascribed to the suppressive tumor environment. We investigated the effects of depleting CD4(+)CD25(+) "natural" regulatory T cells (Treg) on the frequency, phenotype and function of total dendritic cell populations in B16.OVA tumors and in tumor-draining lymph nodes. Intraperitoneal injection of the anti-CD25 monoclonal antibody PC61 reduced Treg frequency in blood and tumors, but did not affect the frequency of tumor-infiltrating dendritic cells, or their expression of CD40, CD86 and MHCII. Tumor-infiltrating dendritic cells from PC61-treated or untreated mice induced the proliferation of allogeneic T cells in vitro, but could not induce proliferation of OVA-specific OTI and OTII T cells unless specific peptide antigen was added in culture. Some proliferation of naïve, OVA-specific OTI T cells, but not OTII T cells, was observed in the tumor-draining LN of mice carrying B16.OVA tumors, however, this was not improved by PC61 treatment. Experiments using RAG1(-/-) hosts adoptively transferred with OTI and CD25-depleted OTII cells also failed to show improved OTI and OTII T cell proliferation in vivo compared to C57BL/6 hosts. We conclude that the defective presentation of B16.OVA tumor antigen by tumor-infiltrating dendritic cells and in the tumor-draining lymph node is not due to the presence of "natural" CD4(+)CD25(+) Treg.
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: Haley
authors.initials: H
authors.lastname: Ataera
authors.forename: Evelyn
authors.initials: E
authors.lastname: Hyde
authors.forename: Kylie M
authors.initials: KM
authors.lastname: Price
authors.forename: Patrizia
authors.initials: P
authors.lastname: Stoitzner
authors.forename: Franca
authors.initials: F
authors.lastname: Ronchese
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008198:Lymph Nodes / Q000473:pathology; D008212:Lymphocyte Depletion; D008545:Melanoma / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018398:Homeodomain Proteins; D053645:Interleukin-2 Receptor alpha Subunit; C064658:RAG-1 protein